Genetic Variant DRD2:p.His313His (chr11-113412755-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000795.4(DRD2):c.939T>C(p.His313His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 1,613,622 control chromosomes in the GnomAD database, including 370,449 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 27670 hom., cov: 31)

Exomes 𝑓: 0.68 ( 342779 hom. )

Consequence

DRD2
NM_000795.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.561

Publications

172 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 11-113412755-A-G is Benign according to our data. Variant chr11-113412755-A-G is described in ClinVar as Benign. ClinVar VariationId is 256814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.561 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.694 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
DRD2	NM_000795.4	MANE Select	c.939T>C	p.His313His	synonymous	Exon 7 of 8	NP_000786.1
DRD2	NM_001440368.1		c.936T>C	p.His312His	synonymous	Exon 7 of 8	NP_001427297.1
DRD2	NM_016574.4		c.852T>C	p.His284His	synonymous	Exon 6 of 7	NP_057658.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DRD2	ENST00000362072.8	TSL:1 MANE Select	c.939T>C	p.His313His	synonymous	Exon 7 of 8	ENSP00000354859.3
DRD2	ENST00000542968.5	TSL:1	c.939T>C	p.His313His	synonymous	Exon 6 of 7	ENSP00000442172.1
DRD2	ENST00000544518.5	TSL:1	c.936T>C	p.His312His	synonymous	Exon 6 of 7	ENSP00000441068.1

Frequencies

GnomAD3 genomes

AF:

0.587

AC:

89038

AN:

151678

Hom.:

27669

Cov.:

show subpopulations

Gnomad AFR

AF:

0.374

Gnomad AMI

AF:

0.711

Gnomad AMR

AF:

0.615

Gnomad ASJ

AF:

0.658

Gnomad EAS

AF:

0.461

Gnomad SAS

AF:

0.612

Gnomad FIN

AF:

0.660

Gnomad MID

AF:

0.620

Gnomad NFE

AF:

0.700

Gnomad OTH

AF:

0.631

GnomAD2 exomes

AF:

0.643

AC:

161575

AN:

251158

AF XY:

0.649

show subpopulations

Gnomad AFR exome

AF:

0.365

Gnomad AMR exome

AF:

0.681

Gnomad ASJ exome

AF:

0.648

Gnomad EAS exome

AF:

0.458

Gnomad FIN exome

AF:

0.659

Gnomad NFE exome

AF:

0.699

Gnomad OTH exome

AF:

0.663

GnomAD4 exome

AF:

0.680

AC:

994750

AN:

1461826

Hom.:

342779

Cov.:

AF XY:

0.680

AC XY:

494465

AN XY:

727212

show subpopulations

African (AFR)

AF:

0.348

AC:

11660

AN:

33476

American (AMR)

AF:

0.672

AC:

30065

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.650

AC:

16977

AN:

26134

East Asian (EAS)

AF:

0.447

AC:

17741

AN:

39698

South Asian (SAS)

AF:

0.632

AC:

54546

AN:

86256

European-Finnish (FIN)

AF:

0.668

AC:

35687

AN:

53410

Middle Eastern (MID)

AF:

0.586

AC:

3381

AN:

5766

European-Non Finnish (NFE)

AF:

0.706

AC:

785154

AN:

1111968

Other (OTH)

AF:

0.655

AC:

39539

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

20702

41405

62107

82810

103512

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19640

39280

58920

78560

98200

<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:

0.587

AC:

89058

AN:

151796

Hom.:

27670

Cov.:

AF XY:

0.585

AC XY:

43387

AN XY:

74186

show subpopulations

African (AFR)

AF:

0.373

AC:

15435

AN:

41336

American (AMR)

AF:

0.615

AC:

9393

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.658

AC:

2279

AN:

3466

East Asian (EAS)

AF:

0.461

AC:

2365

AN:

5128

South Asian (SAS)

AF:

0.614

AC:

2942

AN:

4788

European-Finnish (FIN)

AF:

0.660

AC:

6958

AN:

10544

Middle Eastern (MID)

AF:

0.599

AC:

176

AN:

294

European-Non Finnish (NFE)

AF:

0.700

AC:

47542

AN:

67956

Other (OTH)

AF:

0.629

AC:

1324

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1757

3515

5272

7030

8787

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

752

1504

2256

3008

3760

<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:

0.644

Hom.:

65363

Bravo

AF:

0.578

Asia WGS

AF:

0.518

AC:

1800

AN:

3478

EpiCase

AF:

0.700

EpiControl

AF:

0.709

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 23, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Schizophrenia

Benign:1

Center for Forensic Mental Health, Chiba University

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:case-control

Dystonic disorder

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.020

(source)

DANN

Benign

0.52

PhyloP100

-0.56

Mutation Taster

=100/0

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over