dbSNP rs12363125: DRD2:c.723+227G>A (chr11-113415194-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000795.4(DRD2):c.723+227G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 431,872 control chromosomes in the GnomAD database, including 59,122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.43 ( 16970 hom., cov: 32)

Exomes 𝑓: 0.52 ( 42152 hom. )

Consequence

DRD2
NM_000795.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0550

Publications

19 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 11-113415194-C-T is Benign according to our data. Variant chr11-113415194-C-T is described in ClinVar as Benign. ClinVar VariationId is 1272787.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD2	NM_000795.4 link	c.723+227G>A		intron_variant	Intron 5 of 7	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.723+227G>A		intron_variant	Intron 5 of 7	1	NM_000795.4	ENSP00000354859.3		P14416-1

Frequencies

GnomAD3 genomes

AF:

0.428

AC:

64883

AN:

151750

Hom.:

16982

Cov.:

show subpopulations

Gnomad AFR

AF:

0.169

Gnomad AMI

AF:

0.709

Gnomad AMR

AF:

0.389

Gnomad ASJ

AF:

0.643

Gnomad EAS

AF:

0.0586

Gnomad SAS

AF:

0.364

Gnomad FIN

AF:

0.476

Gnomad MID

AF:

0.573

Gnomad NFE

AF:

0.601

Gnomad OTH

AF:

0.495

GnomAD4 exome

AF:

0.520

AC:

145529

AN:

280004

Hom.:

42152

AF XY:

0.523

AC XY:

74295

AN XY:

141952

show subpopulations

African (AFR)

AF:

0.166

AC:

1339

AN:

8060

American (AMR)

AF:

0.375

AC:

3648

AN:

9716

Ashkenazi Jewish (ASJ)

AF:

0.645

AC:

6210

AN:

9626

East Asian (EAS)

AF:

0.0603

AC:

1435

AN:

23788

South Asian (SAS)

AF:

0.385

AC:

2133

AN:

5540

European-Finnish (FIN)

AF:

0.504

AC:

11049

AN:

21932

Middle Eastern (MID)

AF:

0.561

AC:

754

AN:

1344

European-Non Finnish (NFE)

AF:

0.602

AC:

109880

AN:

182388

Other (OTH)

AF:

0.516

AC:

9081

AN:

17610

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

2861

5722

8584

11445

14306

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

692

1384

2076

2768

3460

<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:

0.427

AC:

64871

AN:

151868

Hom.:

16970

Cov.:

AF XY:

0.417

AC XY:

30969

AN XY:

74214

show subpopulations

African (AFR)

AF:

0.169

AC:

6990

AN:

41464

American (AMR)

AF:

0.388

AC:

5916

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.643

AC:

2230

AN:

3468

East Asian (EAS)

AF:

0.0581

AC:

300

AN:

5160

South Asian (SAS)

AF:

0.364

AC:

1747

AN:

4806

European-Finnish (FIN)

AF:

0.476

AC:

5003

AN:

10502

Middle Eastern (MID)

AF:

0.565

AC:

166

AN:

294

European-Non Finnish (NFE)

AF:

0.601

AC:

40838

AN:

67908

Other (OTH)

AF:

0.491

AC:

1034

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1588

3176

4763

6351

7939

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

580

1160

1740

2320

2900

<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:

0.541

Hom.:

69196

Bravo

AF:

0.412

Asia WGS

AF:

0.202

AC:

702

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 18, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.8

(source)

DANN

Benign

0.75

PhyloP100

-0.055

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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