chr7-6505904-C-T
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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
NM_001145118.2 missense
Scores
3
6
9
Clinical Significance
Conservation
PhyloP100: 4.69
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]
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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 | c.2548G>A | p.Gly850Arg | missense_variant | 14/22 | ENST00000457091.3 | |
LOC101927325 | XR_007060200.1 | n.1394C>T | non_coding_transcript_exon_variant | 1/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRID2IP | ENST00000457091.3 | c.2548G>A | p.Gly850Arg | missense_variant | 14/22 | 5 | NM_001145118.2 | P1 | |
GRID2IP | ENST00000435185.5 | c.1996G>A | p.Gly666Arg | missense_variant | 13/21 | 5 | |||
GRID2IP | ENST00000452113.5 | c.1975G>A | p.Gly659Arg | missense_variant | 13/21 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000854 AC: 13AN: 152194Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000697 AC: 11AN: 157730Hom.: 0 AF XY: 0.0000721 AC XY: 6AN XY: 83196
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GnomAD4 exome AF: 0.0000401 AC: 56AN: 1398006Hom.: 0 Cov.: 30 AF XY: 0.0000406 AC XY: 28AN XY: 689674
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GnomAD4 genome AF: 0.0000854 AC: 13AN: 152312Hom.: 0 Cov.: 33 AF XY: 0.0000671 AC XY: 5AN XY: 74478
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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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Benign
T;T;T
Polyphen
1.0
.;.;D
Vest4
MutPred
0.43
.;.;Gain of solvent accessibility (P = 0.0456);
MVP
MPC
0.37
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: -2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at