Variant rs4986918 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000795.4(DRD2):c.132C>T(p.Leu44=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00343 in 1,614,256 control chromosomes in the GnomAD database, including 162 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 85 hom., cov: 33)

Exomes 𝑓: 0.0018 ( 77 hom. )

Consequence

DRD2
NM_000795.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.59

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 11-113424520-G-A is Benign according to our data. Variant chr11-113424520-G-A is described in ClinVar as [Benign]. Clinvar id is 416374.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.59 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DRD2	NM_000795.4 linkuse as main transcript	c.132C>T	p.Leu44=	synonymous_variant	2/8	ENST00000362072.8
DRD2	NM_016574.4 linkuse as main transcript	c.132C>T	p.Leu44=	synonymous_variant	2/7
DRD2	XM_017017296.3 linkuse as main transcript	c.132C>T	p.Leu44=	synonymous_variant	2/8
DRD2	XM_047426511.1 linkuse as main transcript	c.132C>T	p.Leu44=	synonymous_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRD2	ENST00000362072.8 linkuse as main transcript	c.132C>T	p.Leu44=	synonymous_variant	2/8	1	NM_000795.4	P4	P14416-1

Frequencies

GnomAD3 genomes

AF:

0.0187

AC:

2854

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0658

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00497

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00482

AC:

1211

AN:

251454

Hom.:

AF XY:

0.00344

AC XY:

468

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.0656

Gnomad AMR exome

AF:

0.00304

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000220

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00184

AC:

2686

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00159

AC XY:

1157

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0628

Gnomad4 AMR exome

AF:

0.00344

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000164

Gnomad4 OTH exome

AF:

0.00359

GnomAD4 genome

AF:

0.0187

AC:

2856

AN:

152364

Hom.:

Cov.:

AF XY:

0.0178

AC XY:

1329

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.0657

Gnomad4 AMR

AF:

0.00490

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00991

Hom.:

Bravo

AF:

0.0206

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 09, 2021

- -

Dystonic disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

7.8

DANN

Benign

0.60

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