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GeneBe

3-14509910-C-T

Variant summary

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

The NM_001080423.4(GRIP2):c.1988G>A(p.Gly663Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G663V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

GRIP2
NM_001080423.4 missense

Scores

3
6
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.92
Variant links:
Genes affected
GRIP2 (HGNC:23841): (glutamate receptor interacting protein 2) Predicted to enable protein C-terminus binding activity. Predicted to be involved in several processes, including neurotransmitter receptor transport, endosome to postsynaptic membrane; positive regulation of AMPA glutamate receptor clustering; and positive regulation of excitatory postsynaptic potential. Predicted to act upstream of or within Notch signaling pathway; artery smooth muscle contraction; and positive regulation of blood pressure. Predicted to be located in cytoplasm; dendritic shaft; and neuron spine. Predicted to be active in glutamatergic synapse and postsynaptic density. [provided by Alliance of Genome Resources, Apr 2022]

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
GRIP2NM_001080423.4 linkuse as main transcriptc.1988G>A p.Gly663Glu missense_variant 17/24 ENST00000621039.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GRIP2ENST00000621039.5 linkuse as main transcriptc.1988G>A p.Gly663Glu missense_variant 17/241 NM_001080423.4 P2Q9C0E4-1
GRIP2ENST00000619221.4 linkuse as main transcriptc.2279G>A p.Gly760Glu missense_variant 18/255
GRIP2ENST00000637182.1 linkuse as main transcriptc.2003G>A p.Gly668Glu missense_variant 17/245 A1
GRIP2ENST00000430219.2 linkuse as main transcriptc.365G>A p.Gly122Glu missense_variant, NMD_transcript_variant 5/122

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1398082
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
689462
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

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 submitterclinical testingAmbry GeneticsJan 16, 2024The c.2279G>A (p.G760E) alteration is located in exon 18 (coding exon 18) of the GRIP2 gene. This alteration results from a G to A substitution at nucleotide position 2279, causing the glycine (G) at amino acid position 760 to be replaced by a glutamic acid (E). 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
Pathogenic
0.76
BayesDel_addAF
Pathogenic
0.21
D
BayesDel_noAF
Uncertain
0.060
Cadd
Benign
23
Dann
Benign
0.60
DEOGEN2
Benign
0.12
T;.;.
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Pathogenic
0.99
D;D;D
MetaRNN
Uncertain
0.70
D;D;D
MutationAssessor
Uncertain
2.1
M;.;.
PrimateAI
Uncertain
0.74
T
Sift4G
Uncertain
0.0020
D;D;.
Polyphen
1.0
D;.;.
Vest4
0.43
MVP
0.70
GERP RS
5.1
Varity_R
0.27
gMVP
0.76

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-14551418; API