Genetic Variant NM_000795.4:c.1139-134T>G (chr11-113411054-A-C) – 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.1139-134T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 916,124 control chromosomes in the GnomAD database, including 206,038 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.60 ( 28591 hom., cov: 31)

Exomes 𝑓: 0.68 ( 177447 hom. )

Consequence

DRD2
NM_000795.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.27

Publications

14 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 11-113411054-A-C is Benign according to our data. Variant chr11-113411054-A-C is described in ClinVar as [Benign]. Clinvar id is 1238634.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD2	NM_000795.4 link	c.1139-134T>G		intron_variant	Intron 7 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.1139-134T>G		intron_variant	Intron 7 of 7	1	NM_000795.4	ENSP00000354859.3		P14416-1

Frequencies

GnomAD3 genomes

AF:

0.602

AC:

91332

AN:

151762

Hom.:

28585

Cov.:

show subpopulations

Gnomad AFR

AF:

0.427

Gnomad AMI

AF:

0.711

Gnomad AMR

AF:

0.618

Gnomad ASJ

AF:

0.656

Gnomad EAS

AF:

0.458

Gnomad SAS

AF:

0.627

Gnomad FIN

AF:

0.658

Gnomad MID

AF:

0.627

Gnomad NFE

AF:

0.699

Gnomad OTH

AF:

0.639

GnomAD4 exome

AF:

0.676

AC:

516362

AN:

764244

Hom.:

177447

AF XY:

0.675

AC XY:

260853

AN XY:

386402

show subpopulations

African (AFR)

AF:

0.409

AC:

7496

AN:

18346

American (AMR)

AF:

0.655

AC:

14634

AN:

22326

Ashkenazi Jewish (ASJ)

AF:

0.651

AC:

10370

AN:

15936

East Asian (EAS)

AF:

0.440

AC:

14255

AN:

32426

South Asian (SAS)

AF:

0.646

AC:

34265

AN:

53066

European-Finnish (FIN)

AF:

0.668

AC:

26560

AN:

39732

Middle Eastern (MID)

AF:

0.624

AC:

1691

AN:

2712

European-Non Finnish (NFE)

AF:

0.705

AC:

383397

AN:

543534

Other (OTH)

AF:

0.655

AC:

23694

AN:

36166

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

8004

16007

24011

32014

40018

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.602

AC:

91365

AN:

151880

Hom.:

28591

Cov.:

AF XY:

0.599

AC XY:

44508

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.426

AC:

17664

AN:

41424

American (AMR)

AF:

0.618

AC:

9433

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.656

AC:

2274

AN:

3468

East Asian (EAS)

AF:

0.458

AC:

2340

AN:

5110

South Asian (SAS)

AF:

0.628

AC:

3019

AN:

4804

European-Finnish (FIN)

AF:

0.658

AC:

6960

AN:

10574

Middle Eastern (MID)

AF:

0.605

AC:

178

AN:

294

European-Non Finnish (NFE)

AF:

0.700

AC:

47508

AN:

67912

Other (OTH)

AF:

0.636

AC:

1341

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1790

3581

5371

7162

8952

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.657

Hom.:

48618

Bravo

AF:

0.595

Asia WGS

AF:

0.531

AC:

1848

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

-0.96

CADD

Benign

0.0020

(source)

DANN

Benign

0.58

PhyloP100

-3.3

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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NM_000795.4:c.1139-134T>G

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