rs6277

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000795.4(DRD2):​c.957C>T​(p.Pro319Pro) 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:5

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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank MANE Protein UniProt
DRD2NM_000795.4 linkc.957C>T p.Pro319Pro synonymous_variant Exon 7 of 8 ENST00000362072.8 NP_000786.1 P14416-1A0A024R3C5
DRD2NM_016574.4 linkc.870C>T p.Pro290Pro synonymous_variant Exon 6 of 7 NP_057658.2 P14416-2A0A024R3I6
DRD2XM_017017296.3 linkc.957C>T p.Pro319Pro synonymous_variant Exon 7 of 8 XP_016872785.1 P14416-1A0A024R3C5
DRD2XM_047426511.1 linkc.870C>T p.Pro290Pro synonymous_variant Exon 6 of 7 XP_047282467.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DRD2ENST00000362072.8 linkc.957C>T p.Pro319Pro synonymous_variant Exon 7 of 8 1 NM_000795.4 ENSP00000354859.3 P14416-1

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
GnomAD2 exomes
AF:
0.411
AC:
103247
AN:
251142
AF XY:
0.426
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 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
AC:
3530
AN:
33480
Gnomad4 AMR exome
AF:
0.270
AC:
12086
AN:
44724
Gnomad4 ASJ exome
AF:
0.543
AC:
14202
AN:
26136
Gnomad4 EAS exome
AF:
0.0605
AC:
2402
AN:
39700
Gnomad4 SAS exome
AF:
0.383
AC:
33033
AN:
86256
Gnomad4 FIN exome
AF:
0.470
AC:
25110
AN:
53418
Gnomad4 NFE exome
AF:
0.547
AC:
608510
AN:
1111982
Gnomad4 Remaining exome
AF:
0.473
AC:
28552
AN:
60394
Heterozygous variant carriers
0
24135
48269
72404
96538
120673
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
16736
33472
50208
66944
83680
<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:
0.376
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
AC:
0.125964
AN:
0.125964
Gnomad4 AMR
AF:
0.329
AC:
0.328756
AN:
0.328756
Gnomad4 ASJ
AF:
0.539
AC:
0.539459
AN:
0.539459
Gnomad4 EAS
AF:
0.0592
AC:
0.0592105
AN:
0.0592105
Gnomad4 SAS
AF:
0.351
AC:
0.350728
AN:
0.350728
Gnomad4 FIN
AF:
0.444
AC:
0.444024
AN:
0.444024
Gnomad4 NFE
AF:
0.540
AC:
0.540463
AN:
0.540463
Gnomad4 OTH
AF:
0.429
AC:
0.42925
AN:
0.42925
Heterozygous variant carriers
0
1588
3176
4765
6353
7941
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
536
1072
1608
2144
2680
<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:
0.475
Hom.:
37496
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:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:3
May 21, 2015
Eurofins Ntd Llc (ga)
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Mar 09, 2018
GeneDx
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This 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. -

-
PreventionGenetics, part of Exact Sciences
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

not provided Benign:1
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Dystonic disorder Benign:1
Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
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
-0.78
CADD
Benign
0.79
DANN
Benign
0.75
Mutation Taster
=93/7
polymorphism (auto)

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