rs2283265

Positions:

• chr11-113414814-C-A
• chr11-113414814-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_000795.4(DRD2):​c.724-353G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,140 control chromosomes in the GnomAD database, including 2,539 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (2539 hom., cov: 33)
• Consequence: DRD2 NM_000795.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0690

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BP6: Variant 11-113414814-C-A is Benign according to our data. Variant chr11-113414814-C-A is described in ClinVar as [Benign]. Clinvar id is 1167540.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DRD2	NM_000795.4	c.724-353G>T		intron_variant		ENST00000362072.8	NP_000786.1
DRD2	NM_016574.4	c.723+607G>T		intron_variant			NP_057658.2
DRD2	XM_017017296.3	c.724-353G>T		intron_variant			XP_016872785.1
DRD2	XM_047426511.1	c.723+607G>T		intron_variant			XP_047282467.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRD2	ENST00000362072.8	c.724-353G>T		intron_variant		1	NM_000795.4	ENSP00000354859	P4

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24882 AN: 152022 Hom.: 2530 Cov.: 33

Gnomad AFR AF: 0.0892

Gnomad AMI AF: 0.0967

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.164 AC: 24909 AN: 152140 Hom.: 2539 Cov.: 33 AF XY: 0.172 AC XY: 12778 AN XY: 74386

Gnomad4 AFR AF: 0.0890

Gnomad4 AMR AF: 0.269

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.416

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.212

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.160

Alfa AF: 0.0898 Hom.: 144

Bravo AF: 0.168

Asia WGS AF: 0.315 AC: 1094 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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 15, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	12
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2283265; hg19: chr11-113285536;