NM_000795.4:c.957C>T

Variant names:

• chr11-113412737-G-A
• rs6277
• NM_000795.4:c.957C>T
• DRD2 p.Pro319Pro

GermlineCancer (beta)

Variant summary

Our verdict is Benign.

-8 Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -8 classification points (ACGS-UK Somatic Oncogenicity v2025). B1_StrongB4_Strong

The NM_000795.4(DRD2):c.957C>T (p.Pro319Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The gene DRD2 is a cancer driver gene (CancerMine: 1 driver citations). The variant allele was found at a cumulative frequency of 0.488 (AC=787,261) in the gnomAD database across 1,613,936 control chromosomes, including 206,505 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.546. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign/Likely Benign (★★). The variant has been observed in cBioPortal in 3 samples across 3 studies and 3 cancer types; somatic enrichment level: SUPPORTING_LOW (Observed in a small number of cBioPortal cases.).

• Frequency:
  • Genomes: 𝑓 0.38 (13521 hom., cov: 32)
  • Exomes 𝑓: 0.50 (192984 hom.)
• Consequence: DRD2 NM_000795.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.127
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• combined dystonia

  Inheritance: AD Classification: MODERATE Submitted by: PanelApp Australia

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Benign. The variant received -8 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	B1High frequency in general population		GnomAD effective popmax AF >1% — B1 stand-alone benign; GnomAD effective popmax AF = 0.546 — exceeds 1% threshold (B1 applied)
	B4Synonymous/intronic, no splicing impact		Synonymous/intronic variant with confirmed no splicing impact (B4 strong); Synonymous variant — splicing algorithms confirm no impact on splicing (B4 strong [-4])

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_000795.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	DRD2 NM_000795.4	MANE Select	c.957C>T p.Pro319Pro	synonymous	Exon 7 of 8	Prot: NP_000786.1 UniProt:
	DRD2 NM_001440368.1		c.954C>T p.Pro318Pro	synonymous	Exon 7 of 8	Prot: NP_001427297.1 UniProt:
	DRD2 NM_016574.4		c.870C>T p.Pro290Pro	synonymous	Exon 6 of 7	Prot: NP_057658.2

DRD2 NM_000795.4

MANE Select

HGVSc / HGVSpc.957C>Tp.Pro319Pro

Exon rankExon 7 of 8

synonymous

Prot: NP_000786.1UniProt: P14416-1

DRD2 NM_001440368.1

HGVSc / HGVSpc.954C>Tp.Pro318Pro

Exon rankExon 7 of 8

synonymous

Prot: NP_001427297.1UniProt: F8VUV1

DRD2 NM_016574.4

HGVSc / HGVSpc.870C>Tp.Pro290Pro

Exon rankExon 6 of 7

synonymous

Prot: NP_057658.2

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	DRD2 ENST00000362072.8	TSL:1MANE Select	c.957C>T p.Pro319Pro	synonymous	Exon 7 of 8	Prot: ENSP00000354859.3 UniProt:
	DRD2 ENST00000542968.5	TSL:1	c.957C>T p.Pro319Pro	synonymous	Exon 6 of 7	Prot: ENSP00000442172.1 UniProt:
	DRD2 ENST00000544518.5	TSL:1	c.954C>T p.Pro318Pro	synonymous	Exon 6 of 7	Prot: ENSP00000441068.1 UniProt:

DRD2 ENST00000362072.8

TSL:1MANE Select

HGVSc / HGVSpc.957C>Tp.Pro319Pro

Exon rankExon 7 of 8

synonymous

Prot: ENSP00000354859.3UniProt: P14416-1

DRD2 ENST00000542968.5

TSL:1

HGVSc / HGVSpc.957C>Tp.Pro319Pro

Exon rankExon 6 of 7

synonymous

Prot: ENSP00000442172.1UniProt: P14416-1

DRD2 ENST00000544518.5

TSL:1

HGVSc / HGVSpc.954C>Tp.Pro318Pro

Exon rankExon 6 of 7

synonymous

Prot: ENSP00000441068.1UniProt: F8VUV1

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 6 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.376	AC:57167	Hom:13534	AN:151962	Cov:32
GnomAD2 exomes	AF: 0.411	AC:103247	Hom:	AN:251142	Cov:
GnomAD4 exome	AF: 0.499	AC:730118	Hom:192984	AN:1461856	Cov:93
GnomAD4 genome	AF: 0.376	AC:57143	Hom:13521	AN:152080	Cov:32
TOPMed (Bravo)	AF: 0.358	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.469	AC:153289	Hom:39784	AN:326542	Cov:
Local & regional cohorts 11 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.438	AC:1025	Hom:250	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.0578	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.530	AC:159	Hom:	AN:300	Cov:
ESP6500 (Exome Variant Server)	AF: 0.409	AC:5313	Hom:	AN:12994	Cov:
GenomeAsia100K	AF: 0.193	AC:674	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.0610	AC:443	Hom:	AN:7234	Cov:
Qatari Genome	AF: 0.362	AC:727	Hom:	AN:2010	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.0580	AC:7121	Hom:225	AN:122674	Cov:
Turkish Variome	AF: 0.548	AC:3679	Hom:1031	AN:6712	Cov:
UK10K	AF: 0.552	AC:4176	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.0609	AC:546	Hom:13	AN:8960	Cov:

Showing 17 sources

Case/control cohorts

Cohort	Cases			Controls
	AF	AC	AN	AF	AC	AN
ASC(Autism)	0.545 *	5243	9616	0.553 *	5766	10420
BipEx(Bipolar disorder (including schizoaffective))	0.539	15325	28420	0.542	15625	28844
Epi25(Epilepsy)	0.462	19367	41958	0.467	31245	66888
SCHEMA(Schizophrenia)	0.341	47165	138354	0.380	89745	235966

Showing 4 cohortsAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	1	Dystonic disorder (1)
-	-	1	not provided (1)

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	0.017
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.79
DANN	Benign	0.75
GPN-Star LLR	N/A	3.0
GPN-Star score	N/A	2.7
Mutation Taster	N/A	93/7	polymorphism (auto)
PhyloP100	Benign	-0.13

Showing 8 of 8 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.010
SpliceAI score (max)	Benign	0.010	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs6277;

hg19: chr11-113283459;

COSMIC: COSV60757274;

COSMIC: COSV60757274;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar