Variant chr17-74843252-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000835.6(GRIN2C):c.2885C>T(p.Pro962Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000277 in 758,106 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000066 ( 0 hom. )

Consequence

GRIN2C
NM_000835.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.668

Variant links:

Genes affected

GRIN2C (HGNC:4587): (glutamate ionotropic receptor NMDA type subunit 2C) This gene encodes a subunit of the N-methyl-D-aspartate (NMDA) receptor, which is a subtype of ionotropic glutamate receptor. NMDA receptors are found in the central nervous system, are permeable to cations and have an important role in physiological processes such as learning, memory, and synaptic development. The receptor is a tetramer of different subunits (typically heterodimer of subunit 1 with one or more of subunits 2A-D), forming a channel that is permeable to calcium, potassium, and sodium, and whose properties are determined by subunit composition. Alterations in the subunit composition of the receptor are associated with pathophysiological conditions such as Parkinson's disease, Alzheimer's disease, depression, and schizophrenia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2013]

GRIN2C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.06322199).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIN2C	NM_000835.6 linkuse as main transcript	c.2885C>T	p.Pro962Leu	missense_variant	13/13	ENST00000293190.10	NP_000826.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIN2C	ENST00000293190.10 linkuse as main transcript	c.2885C>T	p.Pro962Leu	missense_variant	13/13	1	NM_000835.6	ENSP00000293190	P1

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

151728

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000984

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000660

AC:

AN:

606378

Hom.:

Cov.:

AF XY:

0.0000132

AC XY:

AN XY:

303740

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000379

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:

0.0000337

GnomAD4 genome

AF:

0.000112

AC:

AN:

151728

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

AN XY:

74124

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.000984

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000110

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

Jun 12, 2023

The c.2885C>T (p.P962L) alteration is located in exon 13 (coding exon 12) of the GRIN2C gene. This alteration results from a C to T substitution at nucleotide position 2885, causing the proline (P) at amino acid position 962 to be replaced by a leucine (L). 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

0.067

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

8.2

DANN

Benign

0.97

DEOGEN2

Benign

0.053

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.58

M_CAP

Benign

0.043

MetaRNN

Benign

0.063

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.55

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.76

PROVEAN

Benign

0.79

REVEL

Benign

0.017

Sift

Uncertain

0.010

Sift4G

Benign

0.19

Polyphen

0.10

Vest4

0.067

MutPred

0.15

Gain of MoRF binding (P = 0.0643);

MVP

0.56

MPC

0.49

ClinPred

0.40

GERP RS

2.4

Varity_R

0.036

gMVP

0.18

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