rs1040443380

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_000835.6(GRIN2C):c.2815C>T(p.Arg939Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000579 in 1,450,474 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 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. R939Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000059 ( 1 hom. )

Consequence

GRIN2C
NM_000835.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.414

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

Alzheimer disease
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

GRIN2C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.075226575).

BS2

High AC in GnomAd4 at 8 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000835.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIN2C	NM_000835.6	MANE Select	c.2815C>T	p.Arg939Trp	missense	Exon 13 of 13	NP_000826.2	Q14957
	GRIN2C	NR_103735.2		n.2968C>T		non_coding_transcript_exon	Exon 13 of 13

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GRIN2C	ENST00000293190.10	TSL:1 MANE Select	c.2815C>T	p.Arg939Trp	missense	Exon 13 of 13	ENSP00000293190.5	Q14957
GRIN2C	ENST00000940919.1		c.2878C>T	p.Arg960Trp	missense	Exon 14 of 14	ENSP00000610978.1
GRIN2C	ENST00000940918.1		c.2839C>T	p.Arg947Trp	missense	Exon 13 of 13	ENSP00000610977.1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000977

AC:

AN:

112554

AF XY:

0.0000973

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000119

Gnomad OTH exome

AF:

0.000279

GnomAD4 exome

AF:

0.0000585

AC:

AN:

1298338

Hom.:

Cov.:

AF XY:

0.0000546

AC XY:

AN XY:

640444

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28494

American (AMR)

AF:

0.000234

AC:

AN:

34238

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23448

East Asian (EAS)

AF:

0.00

AC:

AN:

34194

South Asian (SAS)

AF:

0.0000403

AC:

AN:

74438

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33290

Middle Eastern (MID)

AF:

0.000770

AC:

AN:

3898

European-Non Finnish (NFE)

AF:

0.0000563

AC:

AN:

1011834

Other (OTH)

AF:

0.0000917

AC:

AN:

54504

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.530

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41460

American (AMR)

AF:

0.000196

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68000

Other (OTH)

AF:

0.000478

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000302

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.22

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.55

M_CAP

Benign

0.0062

MetaRNN

Benign

0.075

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.55

PhyloP100

0.41

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-1.6

REVEL

Benign

0.030

Sift

Benign

0.065

Sift4G

Benign

0.18

Polyphen

0.0

Vest4

0.11

MutPred

0.27

Loss of solvent accessibility (P = 0.001)

MVP

0.29

MPC

0.53

ClinPred

0.039

GERP RS

-4.6

Varity_R

0.088

gMVP

0.27

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over