Genetic Variant DRD2:n.34+29A>G (chr11-113475629-T-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 ENST00000907485.1(DRD2):c.-32+29A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0914 in 152,258 control chromosomes in the GnomAD database, including 836 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.091 ( 836 hom., cov: 32)

Exomes 𝑓: 0.047 ( 0 hom. )

Consequence

DRD2
ENST00000907485.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.71

Publications

121 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:

LOC105369501 (HGNC:):

LOC105369501 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 (BayesDel_noAF=-0.85).

BP6

Variant 11-113475629-T-C is Benign according to our data. Variant chr11-113475629-T-C is described in ClinVar as Benign. ClinVar VariationId is 225963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000907485.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DRD2	NM_000795.4	MANE Select	c.-585A>G	upstream_gene	N/A	NP_000786.1	P14416-1
DRD2	NM_001440368.1		c.-585A>G	upstream_gene	N/A	NP_001427297.1
DRD2	NM_016574.4		c.-585A>G	upstream_gene	N/A	NP_057658.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
DRD2	ENST00000540600.5	TSL:1	n.34+29A>G	intron	N/A
DRD2	ENST00000907485.1		c.-32+29A>G	intron	N/A	ENSP00000577544.1
DRD2	ENST00000907486.1		c.-213+29A>G	intron	N/A	ENSP00000577545.1

Frequencies

GnomAD3 genomes

AF:

0.0913

AC:

13881

AN:

152012

Hom.:

828

Cov.:

show subpopulations

Gnomad AFR

AF:

0.154

Gnomad AMI

AF:

0.0573

Gnomad AMR

AF:

0.0662

Gnomad ASJ

AF:

0.0775

Gnomad EAS

AF:

0.176

Gnomad SAS

AF:

0.0762

Gnomad FIN

AF:

0.0918

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.0550

Gnomad OTH

AF:

0.0791

GnomAD4 exome

AF:

0.0469

AC:

AN:

128

Hom.:

Cov.:

AF XY:

0.0556

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.125

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0185

AC:

AN:

108

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.533

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.0915

AC:

13916

AN:

152130

Hom.:

836

Cov.:

AF XY:

0.0929

AC XY:

6907

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.154

AC:

6392

AN:

41494

American (AMR)

AF:

0.0662

AC:

1012

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0775

AC:

269

AN:

3470

East Asian (EAS)

AF:

0.176

AC:

907

AN:

5168

South Asian (SAS)

AF:

0.0763

AC:

367

AN:

4812

European-Finnish (FIN)

AF:

0.0918

AC:

973

AN:

10594

Middle Eastern (MID)

AF:

0.126

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0550

AC:

3739

AN:

67988

Other (OTH)

AF:

0.0797

AC:

168

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

630

1260

1890

2520

3150

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

304

456

608

760

<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:

0.0671

Hom.:

1557

Bravo

AF:

0.0932

Asia WGS

AF:

0.109

AC:

382

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Dystonic disorder (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.5

(source)

DANN

Benign

0.41

PhyloP100

-1.7

PromoterAI

0.0076

Neutral

(source)

Splicing

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