rs1800496

Positions:

chr11-113412766-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_000795.4(DRD2):c.928C>T(p.Pro310Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 1,613,788 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 24 hom. )

Consequence

DRD2
NM_000795.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:3

Conservation

PhyloP100: 0.409

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 made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003302753).

BP6

Variant 11-113412766-G-A is Benign according to our data. Variant chr11-113412766-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 256812.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=2}.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00108 (1572/1461544) while in subpopulation MID AF= 0.0274 (158/5766). AF 95% confidence interval is 0.0239. There are 24 homozygotes in gnomad4_exome. There are 834 alleles in male gnomad4_exome subpopulation. Median coverage is 36. This position pass quality control queck.

BS2

High AC in GnomAd4 at 179 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DRD2	NM_000795.4 linkuse as main transcript	c.928C>T	p.Pro310Ser	missense_variant	7/8	ENST00000362072.8	NP_000786.1
DRD2	NM_016574.4 linkuse as main transcript	c.841C>T	p.Pro281Ser	missense_variant	6/7		NP_057658.2
DRD2	XM_017017296.3 linkuse as main transcript	c.928C>T	p.Pro310Ser	missense_variant	7/8		XP_016872785.1
DRD2	XM_047426511.1 linkuse as main transcript	c.841C>T	p.Pro281Ser	missense_variant	6/7		XP_047282467.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRD2	ENST00000362072.8 linkuse as main transcript	c.928C>T	p.Pro310Ser	missense_variant	7/8	1	NM_000795.4	ENSP00000354859	P4	P14416-1

Frequencies

GnomAD3 genomes

AF:

0.00118

AC:

180

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.0150

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0318

Gnomad NFE

AF:

0.00123

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00158

AC:

398

AN:

251138

Hom.:

AF XY:

0.00175

AC XY:

237

AN XY:

135726

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.0165

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00114

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00120

Gnomad OTH exome

AF:

0.00342

GnomAD4 exome

AF:

0.00108

AC:

1572

AN:

1461544

Hom.:

Cov.:

AF XY:

0.00115

AC XY:

834

AN XY:

727056

show subpopulations

Gnomad4 AFR exome

AF:

0.000777

Gnomad4 AMR exome

AF:

0.00110

Gnomad4 ASJ exome

AF:

0.0168

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00124

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.000578

Gnomad4 OTH exome

AF:

0.00242

GnomAD4 genome

AF:

0.00118

AC:

179

AN:

152244

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.0150

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00124

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00156

Hom.:

Bravo

AF:

0.00121

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000931

AC:

ExAC

AF:

0.00137

AC:

166

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00224

EpiControl

AF:

0.00219

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	DRD2: BP4, BS1 -
Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 06, 2016	- -

DRD2-associated Dystonia

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

New York Genome Center

Jul 09, 2021

- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Dystonic disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 13, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.081

.;T;.;T;.

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.60

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.43

T;.;T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.0033

T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.2

.;L;.;L;.

MutationTaster

Benign

0.86

N;N;N;N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.30

N;N;N;N;N

REVEL

Benign

0.053

Sift

Benign

0.45

T;T;T;T;T

Sift4G

Benign

0.87

T;T;T;T;T

Polyphen

0.0

B;B;B;B;.

Vest4

0.095

MVP

0.64

MPC

0.82

ClinPred

0.0076

GERP RS

1.6

Varity_R

0.032

gMVP

0.28

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over