rs11652088

Variant names:

• chr17-74843693-G-A
• rs11652088
• NM_000835.6:c.2584-140C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GRIN2C	NM_000835.6	c.2584-140C>T		intron_variant	Intron 12 of 12	ENST00000293190.10	NP_000826.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIN2C	ENST00000293190.10	c.2584-140C>T		intron_variant	Intron 12 of 12	1	NM_000835.6	ENSP00000293190.5
GRIN2C	ENST00000584176.1	n.6327-140C>T		intron_variant	Intron 8 of 8	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

African (AFR) AF: 0.261 AC: 5759 AN: 22052

American (AMR) AF: 0.590 AC: 13186 AN: 22350

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 8921 AN: 18954

East Asian (EAS) AF: 0.267 AC: 8884 AN: 33252

South Asian (SAS) AF: 0.443 AC: 27169 AN: 61292

European-Finnish (FIN) AF: 0.645 AC: 20537 AN: 31846

Middle Eastern (MID) AF: 0.392 AC: 1230 AN: 3136

European-Non Finnish (NFE) AF: 0.632 AC: 453550 AN: 717888

Other (OTH) AF: 0.538 AC: 23135 AN: 42962

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

African (AFR) AF: 0.278 AC: 11504 AN: 41436

American (AMR) AF: 0.546 AC: 8349 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.458 AC: 1586 AN: 3466

East Asian (EAS) AF: 0.264 AC: 1359 AN: 5150

South Asian (SAS) AF: 0.419 AC: 2016 AN: 4814

European-Finnish (FIN) AF: 0.640 AC: 6762 AN: 10564

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.631 AC: 42904 AN: 67948

Other (OTH) AF: 0.484 AC: 1020 AN: 2106

Alfa AF: 0.573 Hom.: 6039

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
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11652088; hg19: chr17-72839832;