rs34360565

chr6-101686341-T-C

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_021956.5(GRIK2):c.939T>C(p.Asp313=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00512 in 1,612,992 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0096 (13 hom., cov: 32)
  • Exomes 𝑓: 0.0046 (35 hom.)
• Consequence: GRIK2 NM_021956.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.96

Genes affected

GRIK2 (HGNC:4580): (glutamate ionotropic receptor kainate type subunit 2) Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. This gene product belongs to the kainate family of glutamate receptors, which are composed of four subunits and function as ligand-activated ion channels. The subunit encoded by this gene is subject to RNA editing at multiple sites within the first and second transmembrane domains, which is thought to alter the structure and function of the receptor complex. Alternatively spliced transcript variants encoding different isoforms have also been described for this gene. Mutations in this gene have been associated with autosomal recessive cognitive disability. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 6-101686341-T-C is Benign according to our data. Variant chr6-101686341-T-C is described in ClinVar as [Benign]. Clinvar id is 129177.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.96 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00965 (1469/152232) while in subpopulation AFR AF= 0.0247 (1028/41550). AF 95% confidence interval is 0.0235. There are 13 homozygotes in gnomad4. There are 692 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 13 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIK2	NM_021956.5	c.939T>C	p.Asp313=	synonymous_variant	7/17	ENST00000369134.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIK2	ENST00000369134.9	c.939T>C	p.Asp313=	synonymous_variant	7/17	5	NM_021956.5	P4

Frequencies

GnomAD3 genomes AF: 0.00965 AC: 1468 AN: 152114 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.0248

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00479

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00476

Gnomad OTH AF: 0.00907

GnomAD3 exomes AF: 0.00446 AC: 1119 AN: 251010 Hom.: 8 AF XY: 0.00410 AC XY: 556 AN XY: 135662

Gnomad AFR exome AF: 0.0262

Gnomad AMR exome AF: 0.00269

Gnomad ASJ exome AF: 0.00308

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000294

Gnomad FIN exome AF: 0.000510

Gnomad NFE exome AF: 0.00469

Gnomad OTH exome AF: 0.00294

GnomAD4 exome AF: 0.00465 AC: 6789 AN: 1460760 Hom.: 35 Cov.: 30 AF XY: 0.00451 AC XY: 3278 AN XY: 726744

Gnomad4 AFR exome AF: 0.0251

Gnomad4 AMR exome AF: 0.00297

Gnomad4 ASJ exome AF: 0.00356

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000290

Gnomad4 FIN exome AF: 0.000656

Gnomad4 NFE exome AF: 0.00479

Gnomad4 OTH exome AF: 0.00517

GnomAD4 genome AF: 0.00965 AC: 1469 AN: 152232 Hom.: 13 Cov.: 32 AF XY: 0.00930 AC XY: 692 AN XY: 74434

Gnomad4 AFR AF: 0.0247

Gnomad4 AMR AF: 0.00478

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00104

Gnomad4 NFE AF: 0.00476

Gnomad4 OTH AF: 0.00898

Alfa AF: 0.00716 Hom.: 10

Bravo AF: 0.0108

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.00518

EpiControl AF: 0.00511

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jul 08, 2013

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
Cadd	Benign	11
Dann	Benign	0.56

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: rs34360565; hg19: chr6-102134216;