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GeneBe

rs6277

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000795.4(DRD2):c.957C>T(p.Pro319=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 1,613,936 control chromosomes in the GnomAD database, including 206,505 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 13521 hom., cov: 32)
Exomes 𝑓: 0.50 ( 192984 hom. )

Consequence

DRD2
NM_000795.4 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.127
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
Variant 11-113412737-G-A is Benign according to our data. Variant chr11-113412737-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 198436.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.127 with no splicing effect.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DRD2NM_000795.4 linkuse as main transcriptc.957C>T p.Pro319= synonymous_variant 7/8 ENST00000362072.8
DRD2NM_016574.4 linkuse as main transcriptc.870C>T p.Pro290= synonymous_variant 6/7
DRD2XM_017017296.3 linkuse as main transcriptc.957C>T p.Pro319= synonymous_variant 7/8
DRD2XM_047426511.1 linkuse as main transcriptc.870C>T p.Pro290= synonymous_variant 6/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DRD2ENST00000362072.8 linkuse as main transcriptc.957C>T p.Pro319= synonymous_variant 7/81 NM_000795.4 P4P14416-1

Frequencies

GnomAD3 genomes
AF:
0.376
AC:
57167
AN:
151962
Hom.:
13534
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.126
Gnomad AMI
AF:
0.615
Gnomad AMR
AF:
0.330
Gnomad ASJ
AF:
0.539
Gnomad EAS
AF:
0.0597
Gnomad SAS
AF:
0.351
Gnomad FIN
AF:
0.444
Gnomad MID
AF:
0.494
Gnomad NFE
AF:
0.540
Gnomad OTH
AF:
0.432
GnomAD3 exomes
AF:
0.411
AC:
103247
AN:
251142
Hom.:
24917
AF XY:
0.426
AC XY:
57805
AN XY:
135740
show subpopulations
Gnomad AFR exome
AF:
0.115
Gnomad AMR exome
AF:
0.256
Gnomad ASJ exome
AF:
0.542
Gnomad EAS exome
AF:
0.0568
Gnomad SAS exome
AF:
0.379
Gnomad FIN exome
AF:
0.458
Gnomad NFE exome
AF:
0.543
Gnomad OTH exome
AF:
0.472
GnomAD4 exome
AF:
0.499
AC:
730118
AN:
1461856
Hom.:
192984
Cov.:
93
AF XY:
0.498
AC XY:
362363
AN XY:
727230
show subpopulations
Gnomad4 AFR exome
AF:
0.105
Gnomad4 AMR exome
AF:
0.270
Gnomad4 ASJ exome
AF:
0.543
Gnomad4 EAS exome
AF:
0.0605
Gnomad4 SAS exome
AF:
0.383
Gnomad4 FIN exome
AF:
0.470
Gnomad4 NFE exome
AF:
0.547
Gnomad4 OTH exome
AF:
0.473
GnomAD4 genome
AF:
0.376
AC:
57143
AN:
152080
Hom.:
13521
Cov.:
32
AF XY:
0.368
AC XY:
27371
AN XY:
74356
show subpopulations
Gnomad4 AFR
AF:
0.126
Gnomad4 AMR
AF:
0.329
Gnomad4 ASJ
AF:
0.539
Gnomad4 EAS
AF:
0.0592
Gnomad4 SAS
AF:
0.351
Gnomad4 FIN
AF:
0.444
Gnomad4 NFE
AF:
0.540
Gnomad4 OTH
AF:
0.429
Alfa
AF:
0.471
Hom.:
10466
Bravo
AF:
0.358
Asia WGS
AF:
0.193
AC:
674
AN:
3478
EpiCase
AF:
0.553
EpiControl
AF:
0.561

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:3
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)May 21, 2015- -
Likely benign, criteria provided, single submitterclinical testingGeneDxMar 09, 2018This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Dystonic disorder Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeFeb 01, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
Cadd
Benign
0.79
Dann
Benign
0.75

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs6277; hg19: chr11-113283459; COSMIC: COSV60757274; COSMIC: COSV60757274; API