rs765809246

chr19-48443247-T-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_000836.4(GRIN2D):c.3321T>A(p.Asp1107Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000787 in 1,460,980 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00013 (1 hom., cov: 31)
  • Exomes 𝑓: 0.000073 (1 hom.)
• Consequence: GRIN2D NM_000836.4 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.277

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004858345).
• BP6: Variant 19-48443247-T-A is Benign according to our data. Variant chr19-48443247-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 377345.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd at 19 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIN2D	NM_000836.4	c.3321T>A	p.Asp1107Glu	missense_variant	14/14	ENST00000263269.4
GRIN2D	XM_011526872.2	c.3321T>A	p.Asp1107Glu	missense_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIN2D	ENST00000263269.4	c.3321T>A	p.Asp1107Glu	missense_variant	14/14	1	NM_000836.4	P1

Frequencies

GnomAD3 genomes AF: 0.000129 AC: 19 AN: 147164 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000803

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000904

Gnomad OTH AF: 0.000497

GnomAD3 exomes AF: 0.000416 AC: 58 AN: 139544 Hom.: 1 AF XY: 0.000391 AC XY: 31 AN XY: 79348

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00220

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000781

Gnomad OTH exome AF: 0.000599

GnomAD4 exome AF: 0.0000731 AC: 96 AN: 1313694 Hom.: 1 Cov.: 29 AF XY: 0.0000735 AC XY: 48 AN XY: 652820

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00162

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000365

Gnomad4 OTH exome AF: 0.0000949

GnomAD4 genome AF: 0.000129 AC: 19 AN: 147286 Hom.: 1 Cov.: 31 AF XY: 0.000153 AC XY: 11 AN XY: 71834

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000802

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000904

Gnomad4 OTH AF: 0.000491

Bravo AF: 0.000200

ExAC AF: 0.000225 AC: 25

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jan 05, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Dec 09, 2016	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.71
Cadd	Benign	16
Dann	Benign	0.86
DEOGEN2	Benign	0.098	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.0049	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
MutationTaster	Benign	0.99	N
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.019
Sift	Uncertain	0.0060	D
Sift4G	Benign	1.0	T
Polyphen		0.23	B
Vest4		0.058
MutPred		0.21		Gain of sheet (P = 0.0166);
MVP		0.49
ClinPred		0.016	T
GERP RS		0.58
Varity_R		0.11
gMVP		0.087

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: rs765809246; hg19: chr19-48946504;