rs11652088

Positions:

• chr17-74843693-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000835.6(GRIN2C):​c.2584-140C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 1,105,708 control chromosomes in the GnomAD database, including 193,194 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.50 (21295 hom., cov: 32)
  • Exomes 𝑓: 0.59 (171899 hom.)
• Consequence: GRIN2C NM_000835.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.186

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIN2C	NM_000835.6	c.2584-140C>T		intron_variant		ENST00000293190.10	NP_000826.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIN2C	ENST00000293190.10	c.2584-140C>T		intron_variant		1	NM_000835.6	ENSP00000293190.5
GRIN2C	ENST00000584176.1	n.6327-140C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76275 AN: 151860 Hom.: 21298 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.631

Gnomad OTH AF: 0.487

GnomAD4 exome AF: 0.590 AC: 562371 AN: 953732 Hom.: 171899 AF XY: 0.585 AC XY: 279315 AN XY: 477482

Gnomad4 AFR exome AF: 0.261

Gnomad4 AMR exome AF: 0.590

Gnomad4 ASJ exome AF: 0.471

Gnomad4 EAS exome AF: 0.267

Gnomad4 SAS exome AF: 0.443

Gnomad4 FIN exome AF: 0.645

Gnomad4 NFE exome AF: 0.632

Gnomad4 OTH exome AF: 0.538

GnomAD4 genome AF: 0.502 AC: 76272 AN: 151976 Hom.: 21295 Cov.: 32 AF XY: 0.502 AC XY: 37292 AN XY: 74270

Gnomad4 AFR AF: 0.278

Gnomad4 AMR AF: 0.546

Gnomad4 ASJ AF: 0.458

Gnomad4 EAS AF: 0.264

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.640

Gnomad4 NFE AF: 0.631

Gnomad4 OTH AF: 0.484

Alfa AF: 0.580 Hom.: 6010

Bravo AF: 0.485

Asia WGS AF: 0.354 AC: 1236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.0
DANN	Benign	0.64

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

Other links and lift over

dbSNP: rs11652088; hg19: chr17-72839832;