rs2440390

Variant names:

• chr11-113416156-T-C
• rs2440390
• NM_000795.4:c.533-545A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000795.4(DRD2):​c.533-545A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.867 in 152,240 control chromosomes in the GnomAD database, including 57,376 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.87 (57376 hom., cov: 33)
• Consequence: DRD2 NM_000795.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.18
• Publications: 27 publications found

Genes affected

DRD2 (HGNC:3023): (dopamine receptor D2) This gene encodes the D2 subtype of the dopamine receptor. This G-protein coupled receptor inhibits adenylyl cyclase activity. A missense mutation in this gene causes myoclonus dystonia; other mutations have been associated with schizophrenia. Alternative splicing of this gene results in two transcript variants encoding different isoforms. A third variant has been described, but it has not been determined whether this form is normal or due to aberrant splicing. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 11-113416156-T-C is Benign according to our data. Variant chr11-113416156-T-C is described in ClinVar as Benign. ClinVar VariationId is 1543886.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000795.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD2	NM_000795.4	MANE Select	c.533-545A>G		intron	N/A	NP_000786.1
	DRD2	NM_001440368.1		c.530-545A>G		intron	N/A	NP_001427297.1
	DRD2	NM_016574.4		c.533-545A>G		intron	N/A	NP_057658.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD2	ENST00000362072.8	TSL:1 MANE Select	c.533-545A>G		intron	N/A	ENSP00000354859.3
	DRD2	ENST00000542968.5	TSL:1	c.533-545A>G		intron	N/A	ENSP00000442172.1
	DRD2	ENST00000544518.5	TSL:1	c.530-545A>G		intron	N/A	ENSP00000441068.1

Frequencies

GnomAD3 genomes AF: 0.867 AC: 131950 AN: 152122 Hom.: 57333 Cov.: 33

Gnomad AFR AF: 0.827

Gnomad AMI AF: 0.971

Gnomad AMR AF: 0.897

Gnomad ASJ AF: 0.884

Gnomad EAS AF: 0.962

Gnomad SAS AF: 0.865

Gnomad FIN AF: 0.888

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.873

Gnomad OTH AF: 0.878

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

GnomAD4 genome AF: 0.867 AC: 132047 AN: 152240 Hom.: 57376 Cov.: 33 AF XY: 0.869 AC XY: 64690 AN XY: 74436

African (AFR) AF: 0.827 AC: 34341 AN: 41534

American (AMR) AF: 0.897 AC: 13729 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.884 AC: 3069 AN: 3472

East Asian (EAS) AF: 0.961 AC: 4970 AN: 5170

South Asian (SAS) AF: 0.866 AC: 4178 AN: 4826

European-Finnish (FIN) AF: 0.888 AC: 9411 AN: 10594

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.873 AC: 59374 AN: 68016

Other (OTH) AF: 0.875 AC: 1850 AN: 2114

Alfa AF: 0.870 Hom.: 114753

Bravo AF: 0.869

Asia WGS AF: 0.874 AC: 3039 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Dystonic disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.14
DANN	Benign	0.19
PhyloP100		-1.2
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: rs2440390; hg19: chr11-113286878;