Variant 7-6505904-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001145118.2(GRID2IP):c.2548G>A(p.Gly850Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000445 in 1,550,318 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

GRID2IP
NM_001145118.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.69

Variant links:

Genes affected

GRID2IP (HGNC:18464): (Grid2 interacting protein) Glutamate receptor delta-2 (GRID2; MIM 602368) is predominantly expressed at parallel fiber-Purkinje cell postsynapses and plays crucial roles in synaptogenesis and synaptic plasticity. GRID2IP1 interacts with GRID2 and may control GRID2 signaling in Purkinje cells (Matsuda et al., 2006 [PubMed 16835239]).[supplied by OMIM, Mar 2008]

GRID2IP links:

LOC101927325 (HGNC:):

LOC101927325 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRID2IP	NM_001145118.2 linkuse as main transcript	c.2548G>A	p.Gly850Arg	missense_variant	14/22	ENST00000457091.3
LOC101927325	XR_007060200.1 linkuse as main transcript	n.1394C>T		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GRID2IP	ENST00000457091.3 linkuse as main transcript	c.2548G>A	p.Gly850Arg	missense_variant	14/22	5	NM_001145118.2	P1
GRID2IP	ENST00000435185.5 linkuse as main transcript	c.1996G>A	p.Gly666Arg	missense_variant	13/21	5
GRID2IP	ENST00000452113.5 linkuse as main transcript	c.1975G>A	p.Gly659Arg	missense_variant	13/21	5

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000697

AC:

AN:

157730

Hom.:

AF XY:

0.0000721

AC XY:

AN XY:

83196

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000162

Gnomad ASJ exome

AF:

0.000118

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000878

Gnomad FIN exome

AF:

0.0000592

Gnomad NFE exome

AF:

0.0000327

Gnomad OTH exome

AF:

0.000223

GnomAD4 exome

AF:

0.0000401

AC:

AN:

1398006

Hom.:

Cov.:

AF XY:

0.0000406

AC XY:

AN XY:

689674

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000196

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000560

Gnomad4 SAS exome

AF:

0.0000505

Gnomad4 FIN exome

AF:

0.0000608

Gnomad4 NFE exome

AF:

0.0000353

Gnomad4 OTH exome

AF:

0.0000345

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152312

Hom.:

Cov.:

AF XY:

0.0000671

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000604

ExAC

AF:

0.0000706

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 26, 2021

The c.2548G>A (p.G850R) alteration is located in exon 14 (coding exon 14) of the GRID2IP gene. This alteration results from a G to A substitution at nucleotide position 2548, causing the glycine (G) at amino acid position 850 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.024

T;.;T

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.95

D;D;D

M_CAP

Benign

0.057

MetaRNN

Benign

0.27

T;T;T

MetaSVM

Benign

-0.34

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.92

PROVEAN

Pathogenic

-5.4

D;D;D

REVEL

Uncertain

0.32

Sift

Uncertain

0.017

D;D;D

Sift4G

Benign

0.26

T;T;T

Polyphen

1.0

.;.;D

Vest4

0.35

MutPred

0.43

.;.;Gain of solvent accessibility (P = 0.0456);

MVP

0.54

MPC

0.37

ClinPred

0.89

GERP RS

4.3

Varity_R

0.57

gMVP

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.24

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.24

Position offset: -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