Genetic Variant DRD2:c.*52G>A (chr11-113410675-C-T) – 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.*52G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 1,610,646 control chromosomes in the GnomAD database, including 364,670 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.54 ( 25559 hom., cov: 33)

Exomes 𝑓: 0.68 ( 339111 hom. )

Consequence

DRD2
NM_000795.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.409

Publications

75 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:

ENSG00000256757 (HGNC:):

ENSG00000256757 links:

Genome browser will be placed here

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=-0.83).

BP6

Variant 11-113410675-C-T is Benign according to our data. Variant chr11-113410675-C-T is described in ClinVar as [Benign]. Clinvar id is 1277750.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD2	NM_000795.4 link	c.*52G>A		3_prime_UTR_variant	Exon 8 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.*52G>A		3_prime_UTR_variant	Exon 8 of 8	1	NM_000795.4	ENSP00000354859.3		P14416-1

Frequencies

GnomAD3 genomes

AF:

0.541

AC:

82256

AN:

151940

Hom.:

25557

Cov.:

show subpopulations

Gnomad AFR

AF:

0.218

Gnomad AMI

AF:

0.710

Gnomad AMR

AF:

0.602

Gnomad ASJ

AF:

0.654

Gnomad EAS

AF:

0.459

Gnomad SAS

AF:

0.600

Gnomad FIN

AF:

0.658

Gnomad MID

AF:

0.609

Gnomad NFE

AF:

0.698

Gnomad OTH

AF:

0.599

GnomAD4 exome

AF:

0.675

AC:

984876

AN:

1458588

Hom.:

339111

Cov.:

AF XY:

0.675

AC XY:

489888

AN XY:

725750

show subpopulations

African (AFR)

AF:

0.191

AC:

6396

AN:

33400

American (AMR)

AF:

0.662

AC:

29581

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.647

AC:

16909

AN:

26122

East Asian (EAS)

AF:

0.445

AC:

17655

AN:

39678

South Asian (SAS)

AF:

0.622

AC:

53561

AN:

86064

European-Finnish (FIN)

AF:

0.666

AC:

35502

AN:

53302

Middle Eastern (MID)

AF:

0.591

AC:

3030

AN:

5126

European-Non Finnish (NFE)

AF:

0.706

AC:

783431

AN:

1109966

Other (OTH)

AF:

0.644

AC:

38811

AN:

60224

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

17959

35918

53878

71837

89796

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.541

AC:

82267

AN:

152058

Hom.:

25559

Cov.:

AF XY:

0.541

AC XY:

40214

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.218

AC:

9031

AN:

41466

American (AMR)

AF:

0.602

AC:

9200

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.654

AC:

2268

AN:

3468

East Asian (EAS)

AF:

0.458

AC:

2365

AN:

5160

South Asian (SAS)

AF:

0.601

AC:

2895

AN:

4814

European-Finnish (FIN)

AF:

0.658

AC:

6967

AN:

10590

Middle Eastern (MID)

AF:

0.590

AC:

171

AN:

290

European-Non Finnish (NFE)

AF:

0.698

AC:

47461

AN:

67954

Other (OTH)

AF:

0.597

AC:

1263

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1629

3257

4886

6514

8143

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.593

Hom.:

10414

Bravo

AF:

0.527

Asia WGS

AF:

0.501

AC:

1741

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

-0.83

CADD

Benign

7.7

(source)

DANN

Benign

0.85

PhyloP100

-0.41

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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chr11-113410675-C-T

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