rs1654670

Variant names:

• chr19-48410921-G-C
• rs1654670
• NM_000836.4:c.1086-3070G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-48410921-G-C
• chr19-48410921-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

GRIN2D Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• developmental and epileptic encephalopathy, 46

  Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GRIN2D	NM_000836.4	c.1086-3070G>C		intron_variant	Intron 4 of 13	ENST00000263269.4	NP_000827.2
GRIN2D	XM_011526872.2	c.1086-3070G>C		intron_variant	Intron 2 of 11		XP_011525174.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIN2D	ENST00000263269.4	c.1086-3070G>C		intron_variant	Intron 4 of 13	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

African (AFR) AF: 0.192 AC: 7962 AN: 41454

American (AMR) AF: 0.183 AC: 2795 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 855 AN: 3470

East Asian (EAS) AF: 0.344 AC: 1777 AN: 5168

South Asian (SAS) AF: 0.328 AC: 1579 AN: 4816

European-Finnish (FIN) AF: 0.271 AC: 2868 AN: 10576

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12904 AN: 67972

Other (OTH) AF: 0.218 AC: 458 AN: 2100

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
PhyloP100		-0.025
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: rs1654670; hg19: chr19-48914178;