11-113412737-G-C

Variant names:

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

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-3 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -3 classification points (ACMG Germline Pathogenicity v2019). PM2BP4_StrongBP7

The NM_000795.4(DRD2):c.957C>G (p.Pro319Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DRD2 NM_000795.4 synonymous
• Clinical Significance: Not reported in ClinVar
• 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 ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Likely_benign. The variant received -3 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Absent from gnomAD (AD/XL gene) — PM2; Absent from gnomAD at well-covered site (MOI: AD/XL) (threshold 0.0001) — PM2 moderate.
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).
	BP7Synonymous variant, no splicing impact		Synonymous variant at non-conserved position with no predicted splicing impact (BP7); Synonymous at non-conserved position, no splicing concern — benign (BP7).

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>G p.Pro319Pro	synonymous	Exon 7 of 8	Prot: NP_000786.1 UniProt:
	DRD2 NM_001440368.1		c.954C>G p.Pro318Pro	synonymous	Exon 7 of 8	Prot: NP_001427297.1 UniProt:
	DRD2 NM_016574.4		c.870C>G p.Pro290Pro	synonymous	Exon 6 of 7	Prot: NP_057658.2

DRD2 NM_000795.4

MANE Select

HGVSc / HGVSpc.957C>Gp.Pro319Pro

Exon rankExon 7 of 8

synonymous

Prot: NP_000786.1UniProt: P14416-1

DRD2 NM_001440368.1

HGVSc / HGVSpc.954C>Gp.Pro318Pro

Exon rankExon 7 of 8

synonymous

Prot: NP_001427297.1UniProt: F8VUV1

DRD2 NM_016574.4

HGVSc / HGVSpc.870C>Gp.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>G p.Pro319Pro	synonymous	Exon 7 of 8	Prot: ENSP00000354859.3 UniProt:
	DRD2 ENST00000542968.5	TSL:1	c.957C>G p.Pro319Pro	synonymous	Exon 6 of 7	Prot: ENSP00000442172.1 UniProt:
	DRD2 ENST00000544518.5	TSL:1	c.954C>G p.Pro318Pro	synonymous	Exon 6 of 7	Prot: ENSP00000441068.1 UniProt:

DRD2 ENST00000362072.8

TSL:1MANE Select

HGVSc / HGVSpc.957C>Gp.Pro319Pro

Exon rankExon 7 of 8

synonymous

Prot: ENSP00000354859.3UniProt: P14416-1

DRD2 ENST00000542968.5

TSL:1

HGVSc / HGVSpc.957C>Gp.Pro319Pro

Exon rankExon 6 of 7

synonymous

Prot: ENSP00000442172.1UniProt: P14416-1

DRD2 ENST00000544518.5

TSL:1

HGVSc / HGVSpc.954C>Gp.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 3 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:32
GnomAD4 exome	AF:	AC:	Hom:	AN:	Cov:93
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:32

Showing 3 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	0.018
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.23
DANN	Benign	0.61
GPN-Star LLR	N/A	-1.5
GPN-Star score	N/A	1.5
PhyloP100	Benign	-0.13

Showing 7 of 7 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.020
SpliceAI score (max)	Benign	0.030	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;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar