11-113445514-C-T

Variant names:

• chr11-113445514-C-T
• rs12574471
• NM_000795.4:c.-31-20832G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000795.4(DRD2):​c.-31-20832G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,206 control chromosomes in the GnomAD database, including 867 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 0.11 (867 hom., cov: 32)
• Consequence: DRD2 NM_000795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810
• Publications: 14 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD2	NM_000795.4	c.-31-20832G>A		intron_variant	Intron 1 of 7	ENST00000362072.8	NP_000786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRD2	ENST00000362072.8	c.-31-20832G>A		intron_variant	Intron 1 of 7	1	NM_000795.4	ENSP00000354859.3

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15991 AN: 152088 Hom.: 865 Cov.: 32

Gnomad AFR AF: 0.0817

Gnomad AMI AF: 0.0286

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0833

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.0811

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.108

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

GnomAD4 genome AF: 0.105 AC: 15995 AN: 152206 Hom.: 867 Cov.: 32 AF XY: 0.104 AC XY: 7714 AN XY: 74408

African (AFR) AF: 0.0815 AC: 3383 AN: 41518

American (AMR) AF: 0.105 AC: 1605 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0833 AC: 289 AN: 3470

East Asian (EAS) AF: 0.133 AC: 687 AN: 5166

South Asian (SAS) AF: 0.129 AC: 624 AN: 4828

European-Finnish (FIN) AF: 0.0811 AC: 859 AN: 10592

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8239 AN: 68010

Other (OTH) AF: 0.112 AC: 236 AN: 2116

Alfa AF: 0.116 Hom.: 1591

Bravo AF: 0.105

Asia WGS AF: 0.135 AC: 470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.6
DANN	Benign	0.74
PhyloP100		-0.081
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: rs12574471; hg19: chr11-113316236; COSMIC: COSV60754013; COSMIC: COSV60754013;