7-6503654-G-C

Position:

• chr7-6503654-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001145118.2(GRID2IP):​c.2744C>G​(p.Ala915Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GRID2IP NM_001145118.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.032257736).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRID2IP	NM_001145118.2	c.2744C>G	p.Ala915Gly	missense_variant	16/22	ENST00000457091.3
GRID2IP	NM_001394781.1	c.2195C>G	p.Ala732Gly	missense_variant	15/21
GRID2IP	NM_001388403.1	c.2171C>G	p.Ala724Gly	missense_variant	15/21
GRID2IP	XM_047420365.1	c.2174C>G	p.Ala725Gly	missense_variant	15/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRID2IP	ENST00000457091.3	c.2744C>G	p.Ala915Gly	missense_variant	16/22	5	NM_001145118.2	P1
GRID2IP	ENST00000435185.5	c.2192C>G	p.Ala731Gly	missense_variant	15/21	5
GRID2IP	ENST00000452113.5	c.2171C>G	p.Ala724Gly	missense_variant	15/21	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	19
DANN	Benign	0.84
DEOGEN2	Benign	0.0047	T;.;T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.0023	N
LIST_S2	Benign	0.85	T;T;T
M_CAP	Benign	0.064	D
MetaRNN	Benign	0.032	T;T;T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.54	N;N;N
REVEL	Benign	0.020
Sift	Benign	0.44	T;T;T
Sift4G	Benign	0.67	T;T;T
Polyphen		0.0	.;.;B
Vest4		0.13
MutPred		0.35		.;.;Gain of methylation at K911 (P = 0.0986);
MVP		0.014
MPC		0.21
ClinPred		0.054	T
GERP RS		2.1
Varity_R		0.053
gMVP		0.14

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: chr7-6543285;