Genetic Variant NM_000795.4:c.1139-653A>C (chr11-113411573-T-G) – 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.1139-653A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 152,402 control chromosomes in the GnomAD database, including 27,664 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 27586 hom., cov: 32)

Exomes 𝑓: 0.67 ( 78 hom. )

Consequence

DRD2
NM_000795.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0730

Publications

12 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=-0.98).

BP6

Variant 11-113411573-T-G is Benign according to our data. Variant chr11-113411573-T-G is described in ClinVar as Benign. ClinVar VariationId is 1662326.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.694 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	Effect	Exon Rank	Protein	UniProt
DRD2	NM_000795.4	MANE Select	c.1139-653A>C	intron	N/A	NP_000786.1	P14416-1
DRD2	NM_001440368.1		c.1136-653A>C	intron	N/A	NP_001427297.1
DRD2	NM_016574.4		c.1052-653A>C	intron	N/A	NP_057658.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DRD2	ENST00000362072.8	TSL:1 MANE Select	c.1139-653A>C	intron	N/A	ENSP00000354859.3	P14416-1
DRD2	ENST00000542968.5	TSL:1	c.1139-653A>C	intron	N/A	ENSP00000442172.1	P14416-1
DRD2	ENST00000544518.5	TSL:1	c.1136-653A>C	intron	N/A	ENSP00000441068.1	F8VUV1

Frequencies

GnomAD3 genomes

AF:

0.585

AC:

88916

AN:

151966

Hom.:

27586

Cov.:

show subpopulations

Gnomad AFR

AF:

0.371

Gnomad AMI

AF:

0.711

Gnomad AMR

AF:

0.613

Gnomad ASJ

AF:

0.655

Gnomad EAS

AF:

0.458

Gnomad SAS

AF:

0.600

Gnomad FIN

AF:

0.658

Gnomad MID

AF:

0.620

Gnomad NFE

AF:

0.699

Gnomad OTH

AF:

0.631

GnomAD4 exome

AF:

0.673

AC:

214

AN:

318

Hom.:

Cov.:

AF XY:

0.735

AC XY:

119

AN XY:

162

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.643

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.667

AC:

AN:

European-Finnish (FIN)

AF:

0.909

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.672

AC:

168

AN:

250

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.585

AC:

88935

AN:

152084

Hom.:

27586

Cov.:

AF XY:

0.583

AC XY:

43329

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.370

AC:

15352

AN:

41448

American (AMR)

AF:

0.613

AC:

9376

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.655

AC:

2275

AN:

3472

East Asian (EAS)

AF:

0.458

AC:

2361

AN:

5158

South Asian (SAS)

AF:

0.601

AC:

2892

AN:

4810

European-Finnish (FIN)

AF:

0.658

AC:

6972

AN:

10600

Middle Eastern (MID)

AF:

0.599

AC:

176

AN:

294

European-Non Finnish (NFE)

AF:

0.699

AC:

47561

AN:

67994

Other (OTH)

AF:

0.628

AC:

1323

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1805

3610

5416

7221

9026

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

754

1508

2262

3016

3770

<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:

0.642

Hom.:

53690

Bravo

AF:

0.576

Asia WGS

AF:

0.511

AC:

1775

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)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

3.1

(source)

DANN

Benign

0.39

PhyloP100

-0.073

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

Computational scores

Splicing

Publications

Other links and lift over