Variant 17-74842556-AGCCCCAGAGTCCTGCCCCTGT-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM4BP6BS1BS2

The NM_000835.6(GRIN2C):c.3560_3580delACAGGGGCAGGACTCTGGGGC(p.His1187_Gly1193del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00213 in 777,666 control chromosomes in the GnomAD database, including 21 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0070 ( 16 hom., cov: 34)

Exomes 𝑓: 0.00095 ( 5 hom. )

Consequence

GRIN2C
NM_000835.6 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.82

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 Benign. Variant got -7 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_000835.6.

BP6

Variant 17-74842556-AGCCCCAGAGTCCTGCCCCTGT-A is Benign according to our data. Variant chr17-74842556-AGCCCCAGAGTCCTGCCCCTGT-A is described in ClinVar as [Benign]. Clinvar id is 3052629.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00698 (1061/152092) while in subpopulation AFR AF= 0.0241 (996/41388). AF 95% confidence interval is 0.0228. There are 16 homozygotes in gnomad4. There are 505 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIN2C	NM_000835.6 link	c.3560_3580delACAGGGGCAGGACTCTGGGGC	p.His1187_Gly1193del	disruptive_inframe_deletion	Exon 13 of 13	ENST00000293190.10	NP_000826.2	Q14957A0A8D9PH81O15398

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIN2C	ENST00000293190.10 link	c.3560_3580delACAGGGGCAGGACTCTGGGGC	p.His1187_Gly1193del	disruptive_inframe_deletion	Exon 13 of 13	1	NM_000835.6	ENSP00000293190.5		Q14957

Frequencies

GnomAD3 genomes

AF:

0.00698

AC:

1061

AN:

151974

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00479

GnomAD3 exomes

AF:

0.00155

AC:

372

AN:

240596

Hom.:

AF XY:

0.00128

AC XY:

168

AN XY:

131522

show subpopulations

Gnomad AFR exome

AF:

0.0210

Gnomad AMR exome

AF:

0.00136

Gnomad ASJ exome

AF:

0.000102

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000233

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000373

Gnomad OTH exome

AF:

0.000509

GnomAD4 exome

AF:

0.000948

AC:

593

AN:

625574

Hom.:

AF XY:

0.000816

AC XY:

278

AN XY:

340740

show subpopulations

Gnomad4 AFR exome

AF:

0.0231

Gnomad4 AMR exome

AF:

0.00184

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000303

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000744

Gnomad4 OTH exome

AF:

0.00167

GnomAD4 genome

AF:

0.00698

AC:

1061

AN:

152092

Hom.:

Cov.:

AF XY:

0.00679

AC XY:

505

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0241

Gnomad4 AMR

AF:

0.00327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00474

Alfa

AF:

0.00347

Hom.:

Bravo

AF:

0.00822

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

GRIN2C-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 15, 2020

This variant is classified as 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