11-113412715-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_000795.4(DRD2):c.979A>G(p.Lys327Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00312 in 1,614,202 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0036 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0031 ( 22 hom. )

Consequence

DRD2
NM_000795.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 8.02

Publications

7 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006436944).

BP6

Variant 11-113412715-T-C is Benign according to our data. Variant chr11-113412715-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 238186.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 541 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD2	NM_000795.4 link	c.979A>G	p.Lys327Glu	missense_variant	Exon 7 of 8	ENST00000362072.8	NP_000786.1	P14416-1A0A024R3C5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRD2	ENST00000362072.8 link	c.979A>G	p.Lys327Glu	missense_variant	Exon 7 of 8	1	NM_000795.4	ENSP00000354859.3		P14416-1

Frequencies

GnomAD3 genomes

AF:

0.00354

AC:

539

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.0205

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00389

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00378

AC:

949

AN:

251342

AF XY:

0.00386

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.000695

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0205

Gnomad NFE exome

AF:

0.00325

Gnomad OTH exome

AF:

0.00489

GnomAD4 exome

AF:

0.00307

AC:

4491

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00312

AC XY:

2267

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.000418

AC:

AN:

33480

American (AMR)

AF:

0.000492

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00227

AC:

196

AN:

86258

European-Finnish (FIN)

AF:

0.0207

AC:

1106

AN:

53420

Middle Eastern (MID)

AF:

0.000693

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00267

AC:

2967

AN:

1112010

Other (OTH)

AF:

0.00285

AC:

172

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

321

643

964

1286

1607

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

220

330

440

550

<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:

0.00355

AC:

541

AN:

152310

Hom.:

Cov.:

AF XY:

0.00427

AC XY:

318

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.000698

AC:

AN:

41562

American (AMR)

AF:

0.000392

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5172

South Asian (SAS)

AF:

0.00249

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0205

AC:

218

AN:

10614

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00389

AC:

265

AN:

68042

Other (OTH)

AF:

0.00331

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

116

145

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00245

Hom.:

Bravo

AF:

0.00151

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.000682

AC:

ESP6500EA

AF:

0.00349

AC:

ExAC

AF:

0.00381

AC:

463

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00251

EpiControl

AF:

0.00219

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Oct 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

DRD2: BS1 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dystonic disorder

Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.14

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

.;T;.;T;.

Eigen

Benign

-0.0048

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.86

D;.;D;D;D

MetaRNN

Benign

0.0064

T;T;T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

1.4

.;L;.;L;.

PhyloP100

8.0

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.57

N;N;N;N;N

REVEL

Benign

0.21

Sift

Benign

0.31

T;T;T;T;T

Sift4G

Benign

0.71

T;T;T;T;T

Polyphen

0.0070

B;B;B;B;.

Vest4

0.49

MVP

0.84

MPC

1.3

ClinPred

0.050

GERP RS

6.0

Varity_R

0.30

gMVP

0.48

Mutation Taster

=68/32

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over