Genetic Variant DRD2:p.Ser311Cys (chr11-113412762-G-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000795.4(DRD2):c.932C>G(p.Ser311Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0232 in 1,613,788 control chromosomes in the GnomAD database, including 590 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 36 hom., cov: 32)

Exomes 𝑓: 0.024 ( 554 hom. )

Consequence

DRD2
NM_000795.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 5.72

Publications

217 publications found

Variant links:

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]

DRD2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0033855736).

BP6

Variant 11-113412762-G-C is Benign according to our data. Variant chr11-113412762-G-C is described in ClinVar as Benign. ClinVar VariationId is 256813.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0589 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DRD2	NM_000795.4	MANE Select	c.932C>G	p.Ser311Cys	missense	Exon 7 of 8	NP_000786.1	P14416-1
DRD2	NM_001440368.1		c.929C>G	p.Ser310Cys	missense	Exon 7 of 8	NP_001427297.1
DRD2	NM_016574.4		c.845C>G	p.Ser282Cys	missense	Exon 6 of 7	NP_057658.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DRD2	ENST00000362072.8	TSL:1 MANE Select	c.932C>G	p.Ser311Cys	missense	Exon 7 of 8	ENSP00000354859.3	P14416-1
DRD2	ENST00000542968.5	TSL:1	c.932C>G	p.Ser311Cys	missense	Exon 6 of 7	ENSP00000442172.1	P14416-1
DRD2	ENST00000544518.5	TSL:1	c.929C>G	p.Ser310Cys	missense	Exon 6 of 7	ENSP00000441068.1	F8VUV1

Frequencies

GnomAD3 genomes

AF:

0.0190

AC:

2886

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00439

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0221

Gnomad ASJ

AF:

0.0363

Gnomad EAS

AF:

0.0332

Gnomad SAS

AF:

0.0652

Gnomad FIN

AF:

0.0185

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0220

Gnomad OTH

AF:

0.0201

GnomAD2 exomes

AF:

0.0266

AC:

6671

AN:

251194

AF XY:

0.0282

show subpopulations

Gnomad AFR exome

AF:

0.00418

Gnomad AMR exome

AF:

0.0213

Gnomad ASJ exome

AF:

0.0391

Gnomad EAS exome

AF:

0.0354

Gnomad FIN exome

AF:

0.0226

Gnomad NFE exome

AF:

0.0206

Gnomad OTH exome

AF:

0.0290

GnomAD4 exome

AF:

0.0236

AC:

34562

AN:

1461568

Hom.:

554

Cov.:

AF XY:

0.0247

AC XY:

17946

AN XY:

727072

show subpopulations

African (AFR)

AF:

0.00323

AC:

108

AN:

33478

American (AMR)

AF:

0.0213

AC:

954

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0385

AC:

1007

AN:

26132

East Asian (EAS)

AF:

0.0349

AC:

1384

AN:

39700

South Asian (SAS)

AF:

0.0590

AC:

5088

AN:

86242

European-Finnish (FIN)

AF:

0.0230

AC:

1229

AN:

53410

Middle Eastern (MID)

AF:

0.0485

AC:

280

AN:

5768

European-Non Finnish (NFE)

AF:

0.0205

AC:

22812

AN:

1111742

Other (OTH)

AF:

0.0282

AC:

1700

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

2397

4794

7192

9589

11986

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

942

1884

2826

3768

4710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0189

AC:

2883

AN:

152220

Hom.:

Cov.:

AF XY:

0.0198

AC XY:

1471

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.00438

AC:

182

AN:

41542

American (AMR)

AF:

0.0222

AC:

340

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0363

AC:

126

AN:

3470

East Asian (EAS)

AF:

0.0331

AC:

171

AN:

5164

South Asian (SAS)

AF:

0.0649

AC:

312

AN:

4810

European-Finnish (FIN)

AF:

0.0185

AC:

196

AN:

10618

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0220

AC:

1494

AN:

68002

Other (OTH)

AF:

0.0199

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

142

284

426

568

710

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0237

Hom.:

Bravo

AF:

0.0174

TwinsUK

AF:

0.0175

AC:

ALSPAC

AF:

0.0202

AC:

ESP6500AA

AF:

0.00636

AC:

ESP6500EA

AF:

0.0223

AC:

192

ExAC

AF:

0.0264

AC:

3203

Asia WGS

AF:

0.0650

AC:

224

AN:

3478

EpiCase

AF:

0.0245

EpiControl

AF:

0.0206

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Dystonic disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.77

MetaRNN

Benign

0.0034

MetaSVM

Benign

-0.42

MutationAssessor

Uncertain

2.5

PhyloP100

5.7

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.41

REVEL

Benign

0.23

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.027

Polyphen

0.036

Vest4

0.32

MPC

1.8

ClinPred

0.019

GERP RS

5.7

Varity_R

0.15

gMVP

0.40

Mutation Taster

=91/9

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over