19-48410921-G-C

Position:

• chr19-48410921-G-C

Variant summary

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

The NM_000836.4(GRIN2D):​c.1086-3070G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 151,994 control chromosomes in the GnomAD database, including 3,439 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 0.21 (3439 hom., cov: 30)
• Consequence: GRIN2D NM_000836.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0250

Genes affected

GRIN2D (HGNC:4588): (glutamate ionotropic receptor NMDA type subunit 2D) N-methyl-D-aspartate (NMDA) receptors are a class of ionotropic glutamate receptors. NMDA channel has been shown to be involved in long-term potentiation, an activity-dependent increase in the efficiency of synaptic transmission thought to underlie certain kinds of memory and learning. NMDA receptor channels are heteromers composed of the key receptor subunit NMDAR1 (GRIN1) and 1 or more of the 4 NMDAR2 subunits: NMDAR2A (GRIN2A), NMDAR2B (GRIN2B), NMDAR2C (GRIN2C), and NMDAR2D (GRIN2D). [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIN2D	NM_000836.4	c.1086-3070G>C		intron_variant		ENST00000263269.4	NP_000827.2
GRIN2D	XM_011526872.2	c.1086-3070G>C		intron_variant			XP_011525174.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIN2D	ENST00000263269.4	c.1086-3070G>C		intron_variant		1	NM_000836.4	ENSP00000263269.2

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31397 AN: 151876 Hom.: 3432 Cov.: 30

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.210

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.207 AC: 31414 AN: 151994 Hom.: 3439 Cov.: 30 AF XY: 0.214 AC XY: 15909 AN XY: 74298

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.344

Gnomad4 SAS AF: 0.328

Gnomad4 FIN AF: 0.271

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.218

Alfa AF: 0.184 Hom.: 301

Bravo AF: 0.197

Asia WGS AF: 0.305 AC: 1059 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.68

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: rs1654670; hg19: chr19-48914178;