rs2440390

chr11-113416156-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DRD2	NM_000795.4	c.533-545A>G		intron_variant		ENST00000362072.8
DRD2	NM_016574.4	c.533-545A>G		intron_variant
DRD2	XM_017017296.3	c.533-545A>G		intron_variant
DRD2	XM_047426511.1	c.533-545A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRD2	ENST00000362072.8	c.533-545A>G		intron_variant		1	NM_000795.4	P4

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

Gnomad4 AFR AF: 0.827

Gnomad4 AMR AF: 0.897

Gnomad4 ASJ AF: 0.884

Gnomad4 EAS AF: 0.961

Gnomad4 SAS AF: 0.866

Gnomad4 FIN AF: 0.888

Gnomad4 NFE AF: 0.873

Gnomad4 OTH AF: 0.875

Alfa AF: 0.870 Hom.: 25556

Bravo AF: 0.869

Asia WGS AF: 0.874 AC: 3039 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Dystonic disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.14
Dann	Benign	0.19

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: rs2440390; hg19: chr11-113286878;