Variant chr17-74842569-T-TGCCCCTGTGCCCCAGAGGCCC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PM4BP6

The NM_000835.6(GRIN2C):c.3567_3568insGGGCCTCTGGGGCACAGGGGC(p.Gly1183_Gly1189dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000293 in 772,044 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00011 ( 1 hom. )

Consequence

GRIN2C
NM_000835.6 inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.287

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM4

Nonframeshift variant in NON repetitive region in NM_000835.6.

BP6

Variant 17-74842569-T-TGCCCCTGTGCCCCAGAGGCCC is Benign according to our data. Variant chr17-74842569-T-TGCCCCTGTGCCCCAGAGGCCC is described in ClinVar as [Likely_benign]. Clinvar id is 3047243.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIN2C	NM_000835.6 linkuse as main transcript	c.3567_3568insGGGCCTCTGGGGCACAGGGGC	p.Gly1183_Gly1189dup	inframe_insertion	13/13	ENST00000293190.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIN2C	ENST00000293190.10 linkuse as main transcript	c.3567_3568insGGGCCTCTGGGGCACAGGGGC	p.Gly1183_Gly1189dup	inframe_insertion	13/13	1	NM_000835.6	P1

Frequencies

GnomAD3 genomes

AF:

0.00103

AC:

155

AN:

150088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00372

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

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:

0.0000294

Gnomad OTH

AF:

0.00145

GnomAD3 exomes

AF:

0.000146

AC:

AN:

233334

Hom.:

AF XY:

0.000117

AC XY:

AN XY:

127866

show subpopulations

Gnomad AFR exome

AF:

0.00230

Gnomad AMR exome

AF:

0.0000299

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000492

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000114

AC:

AN:

621838

Hom.:

Cov.:

AF XY:

0.0000886

AC XY:

AN XY:

338636

show subpopulations

Gnomad4 AFR exome

AF:

0.00346

Gnomad4 AMR exome

AF:

0.0000465

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000194

Gnomad4 NFE exome

AF:

0.0000172

Gnomad4 OTH exome

AF:

0.000122

GnomAD4 genome

AF:

0.00103

AC:

155

AN:

150206

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

AN XY:

73480

show subpopulations

Gnomad4 AFR

AF:

0.00371

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.000927

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

GRIN2C-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 14, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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